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Toxicological information

Acute Toxicity: dermal

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Administrative data

Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Study period:
11th to 25th June 1985
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: The study was not conducted in accordance with a recognised guideline, however the study is detailed with good scientific principles and is similar to OECD 402. Only a single limit dose of 5g/kg was used.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1986
Report Date:
1986

Materials and methods

Test guideline
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Deviations:
not specified
GLP compliance:
yes
Test type:
standard acute method
Limit test:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name and of test material (as cited in study report): Phenol, tetrapropenyl-, sulfurized, carbonates, calcium salts, overbased
- CAS number of test material (as cited in study report): 122384-87-6
Test Material Purity: 100%

Test animals

Species:
rabbit
Strain:
New Zealand White
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: L.I.T. Rabbitry, Whitehall, Montana
- Age at study initiation: The males/females were 18-20 weeks of age at the time of dosing.
- Weight at study initiation: The males weighed 3.11-3.64 kilograms, and the females weighed 2.91-3.58 kilograms at the time of dosing.
- Housing: The animals were housed individually in wire-bottom cages in an air-conditioned room.
- Diet (e.g. ad libitum): The animals were fed a daily ration of Purina Laboratory Rabbit Chow HF #5326.
- Water (e.g. ad libitum): Free access to water.
- Acclimation period: conditioning period of 10 weeks prior to dosing in the laboratory.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22.5-22.8°C
- Humidity (%): 57.7-69.6%
- Photoperiod (hrs dark / hrs light): The photoperiod was a 12-hour light/dark cycle: lights on at 0630 and off at 1830.

Administration / exposure

Type of coverage:
occlusive
Vehicle:
other: Mineral oil (1.0 mL/kg)
Details on dermal exposure:
The fur on the trunks of five animals of each sex was clipped on the day prior to dosing. Five grams per kilogram of body weight of 80% of the test material w/w in mineral oil (4.0 g/kg test material) were applied to the trunk of each animal. This dose level was considered to be the highest dose level practical based on the dose volume that could be contained under the wrap. The material was held in contact with the animal's skin by a plastic sheet wrapped around the animal's trunk, and paper toweling was wrapped over the plastic sheet to prevent tearing. The mean volumes (+S.D.) of test material administered were 14.9 (0.7) ml for males and 14.9 (1.0) ml for females; the mean weights (+S.D.) of test material administered were 16.4 (0.9) g for males and 16.4 (1.1) g for females. Five clipped animals of each sex, treated with 1.0 ml/kg of mineral oil, were wrapped as described above and served as the controls. This volume was equal to the amount of mineral oil contained in the dosing mixture. All animals were collared during the exposure period to prevent damage to the wraps. The animals were dosed and wrapped approximately 4.5 hours after the onset of the light cycle.

After a 24-hour exposure period, the wrappings were removed from the animals. Any remaining test material was wiped off with a gauze pad and mineral oil. Collars remained on treated animals for 24 hours to prevent oral ingestion of residual test material and on controls for the same length of time.
Duration of exposure:
24 hours
Doses:
5g/kg of an 80% suspension of test material in mineral oil.
No. of animals per sex per dose:
5 per sex per dose
Control animals:
yes, concurrent vehicle
Details on study design:
- Duration of observation period following administration: The animals were observed frequently for any physiological or behavioral abnormalities on the day of dosing and at least once each weekday morning and late afternoon for 13 days after treatment; on weekends, they were observed once daily. On Day 14, the animals were observed once prior to sacrifice.

The skin at the application site was scored for irritation at 1, 7, and 14 days after treatment using the modified scoring system of Draize et al.

- Frequency of observations and weighing: The animals were weighed immediately prior to dosing and at 2, 7, and 14 days after treatment. The mean body weights of the treated animals were compared to those of the respective controls using Student's t-test.

- Necropsy of survivors performed: yes, all survivors killed following the 14-day observation period were examined for gross pathological changes. The following organs and tissues were examined: skin, spleen, pancreas, stomach, small and large intestine, liver, adrenals, kidneys, gonads, uterus or seminal vesicles, bladder, heart, thymus, salivary glands, lungs, trachea, thyroid, and fat. Sections of skin from each animal and any abnormal tissues were preserved in 10% (v/v) neutral buffered formalin and submitted for histopathological examination.

- Other examinations performed: Tissues were submitted to Histopathology Reference Laboratory, Oakland, California, for tissue processing and preparation of routine five-micron H&E stained sections. Tissue sections were evaluated for microscopic abnormalities at Chevron Environmental Health Center, Inc.
Statistics:
No data

Results and discussion

Effect levels
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 4 000 mg/kg bw
Based on:
other: 80% solution of the test material in mineral oil
Mortality:
No mortality.
Clinical signs:
Signs of toxicity observed during the study included dry and flaky skin and/or scabbed skin at the application site of all test material treated animals.Skin reactions at the site of application of the test material consisted of slight to moderate erythema with no to well defined edema in both sexes at
24 hours post dosing. On day 7 no to severe erythema with no to well defined edema was observed. Two males and four females exhibited eschar
formation. No irritation was evident in treated skin on day 14. Two vehicle control animals exhibited slight erythema or edema 24 hours after dosing. There were no findings in the vehicle controls on day 7 or 14.
Body weight:
Body weights were unremarkable.
Gross pathology:
The only compound related gross pathology changes observed at necropsy were dry and flaky skin in all treated animals. Histologically, minimal
acanthosis and/or hyperkeratosis were observed in all but one of the treated animals.
Other findings:
Other gross pathological signs observed at necropsy were scratch-like marks on both corneas, a single opaque and vascularized cornea, and white cheesy material at the site of the missing right salivary gland in one control animal. Histologically, chronic keratitis in one eye and abscess in the salivary gland were observed.

Any other information on results incl. tables

The test article, when administered dermally to 5 male and 5 female New Zealand white rabbits had an acute dermal LD50 of greater than 5 g/kg when administered as an 80% suspension of test material in mineral oil. 

Applicant's summary and conclusion

Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The test article, when administered dermally to 5 male and 5 female New Zealand white rabbits had an acute dermal LD50 of greater than 5 g/kg when administered as an 80% suspension of test material in mineral oil.
Executive summary:

In a study conducted broadly in broadly in line with OECD 402 and under conditions of GLP, five adult rabbits of each sex were treated with a single dermal application of 5.0 g/kg of 80% of the test material weight/weight in mineral oil (4.0 g/kg test material). The test material was diluted due to its high viscosity. This dose level was considered to be the highest level practical based on the dose volume that could be contained under the wrap.

No mortality was observed. Signs of toxicity observed during the study were dry and flaky and/or scabbed skin at the application site and reduced food intake.

The only compound-related gross pathological change observed at necropsy was dry and flaky skin at the application site of all treated animals. Upon histological evaluation, minimal acanthosis and/or hyperkeratosis was observed in all but one of the treated animals.

The test article, when administered dermally to 5 male and 5 female New Zealand white rabbits had an acute dermal LD50 of greater than 5 g/kg when administered as an 80% suspension of test material in mineral oil.